Clinical PresentationNCT06680401
Epithelioid Haemangioendothelioma Observational Study
An observational study of Clinical Presentation and Natural History, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
The EHE observational study was developed to obtain a high number of datas such as clinical presentation, natural history, and treatment outcomes, cto identificate cytokines and hormones as biomarkers and generate patient-derived preclinical models as a tool to assess the activity of anticancer agents and validate… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clinical Presentation, Natural History, Treatment Outcomes
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 25 Feb 2021to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: We plan to include at least 50 patients (range: 50-70) in 36 months, followed by a follow up time of 3 years.68 including The Royal Marsden Hospital.
Who may be able to join
- Histological diagnosis of EHE according to 2020 WHO classification, performed on biopsy or surgical specimen
- Signed informed consent
- Adequate patient compliance to treatment or follow up
- No age limit
Who cannot join
- Impossibility to ensure adequate compliance
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS IstitutoNazionale dei Tumori
Milan, 20133
Silvia Stacchiotti, Silvia.Stacchiotti@istitutotumori.mi.it
Anna Maria Frezza, annamaria.frezza@istitutotumori.mi.it
About this study
Official title: The Evaluation of Cytokines and Hormones as Biomarkers for Epithelioid Haemangioendothelioma and Generation of Patient-derived Preclinical Models to Assess the Activity of Anticancer Agents and Validate Novel Therapeutic Targets
The EHE observational study was developed to obtain a high number of datas such as clinical presentation, natural history, and treatment outcomes, cto identificate cytokines and hormones as biomarkers and generate patient-derived preclinical models as a tool to assess the activity of anticancer agents and validate novel therapeutic targets
Read the detailed description
Epithelioid hemangioendothelioma (EHE) is an ultra-rare (incidence rate < 1/1000.000), translocated, vascular soft tissue sarcoma. It shows a pick of incidence in the 4th decade of life, and it is more commonly diagnosed in females, with reported disease onset during pregnancy.
Two specific translocations have been identified in EHE, representing an hallmark in diagnosis today: the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1) which is present in almost 90 % of cases, and the fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3), which can be found in around 10% of the patients. YAP and TAZ are well-defined downstream effectors in the Hippo pathway. Forced activation of YAP/TAZ is thought to drive EHE and contribute to key aspects of the cancer phenotype, including metastasis and fibrosis.
Most of the times, EHE presents as multifocal or metastatic at diagnosis, with lung, liver and bone being the more commonly involved. The clinical course ranges from cases naturally stable over time to those highly aggressive and rapidly fatal. Pleural effusion, lymph node metastases and pathologic features (nuclear pleomorphism, mitotic figures and presence of necrosis) have been reported to be associated with a worse outcome, but biological and molecular predictors are still lacking. In particular, there is a subgroup of EHE presenting with serosal involvement, typically associated with chronic mild fever, weight loss, asthenia, anorexia, severe disease- related pain, (more responsive to anti-inflammatory pain killers that morphine), and dyspnoea which seems to perform very poorly. The biological basis sustaining this presentation is completely unknown.
As of today, there are no reports available in literature providing a comprehensive description of the peculiar EHE radiological features, both for primary and metastatic disease at different sites, and their potential prognostic role has not been explored. In addition, there are no published data to indicate the optimal routine follow-up policy of surgically treated EHE patients with localised disease and the routine follow-up schedules differ across institutions. The appropriate frequency of imaging in cases suffering of distant metastases is also left to be determined.
Also, the definition of radiological progression and the assessment of treatment response in EHE remain major challenges. The appearance or worsening of serosal effusion, the changes in serosal involvement and the limited increase in size over a short-time interval in slow-growing variants are not promptly captured by Response Evaluation Criteria for Solid Tumor (RECIST) definition for disease progression. This makes the use of such criteria unsatisfactory in this complex disease and could potentially lead to a delay in progression recognition and treatment start. Similarly, being frequently observed in EHE under treatment, improvement of serosal effusion, reduction in size <30%, and correlation between radiology and symptoms should be taken into account when assessing treatment response.
Surgery is the mainstay of care in the local setting. Active surveillance can be a reasonable strategy for patients with naturally stable or asymptomatic, slowly progressive disease, reserving medical treatment to symptomatic or progressive cases.
Data on conventional chemotherapy in advanced EHE are limited to case reports and single-institution experiences and suggest a limited role for the drugs commonly used in adult-type soft tissue sarcomas. Signs of activity have been reported with the use of anti-angiogenics, including pazopanib, sorafenib, bevacizumab, alone or in combination with chemotherapy, and apatinib. Due to the peculiar natural history of the disease, the value of antiangiogenics and/or immunomodulatory agents has also been explored, with responses described with sirolimus, thalidomide, interferon, and celecoxib.
In absence of any active treatment available, EHE is a neglected disease, and the identification of new potentially active compounds, especially for patients affected by the more aggressive EHE variant. To this end, it looks to be of major importance to identify what is behind disease progression, the "inflammatory-like" disease presentation, and the prevalence of the disease in the female young population.
Several lines of evidence have highlighted the significance of inflammation at the local and/or systemic level in human tumor pathobiology. Indeed, inflammation can influence tumor progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation.
Estrogen signaling is mediated via several receptor proteins. In addition to the classical ERα and ERβ, the membrane-bound G-protein coupled estrogen receptor (GPER) mediates both the genomic and non-genomic effects of estrogen and has been implicated in the development of other tumors such as breast cancer. Interestingly, GPER stimulation activates YAP and TAZ as key effectors of the Hippo pathway. Insulin-like growth factor-1(IGF-1) has also been shown to regulate GPER expression and function, suggesting a crosstalk between growth factors and ERs The availability of translatable preclinical models of human EHE, able to properly recapitulate tumor biology and response to treatment of the clinical tumors, appears instrumental for the development of innovative and effective treatments. Patient-derived xenograft (PDX) models preserve the original histomorphological and molecular characteristics of the originating clinical tumors. We previously demonstrated the consistency between preclinical data obtained on PDXs of different soft-tissue sarcoma histotypes (solitary fibrous tumor, epithelioid sarcoma and dedifferentiated liposarcoma) and clinical results concerning the activity of several cytotoxic and molecularly targeted drugs, providing novel insight into the antitumor effect of different combinations that was instrumental to design novel clinical trials.
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Their proven deregulation in several types of human cancer, and the possibility to be reliably detected in both tissue and blood specimens, have prompted the assessment of miRNAs as novel cancer biomarkers21. No information is currently available on miRNA expression and function in EHE.
- Conditions
- Clinical Presentation, Natural History, Treatment Outcomes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Patients newly diagnosed with advanced EE starting active surveillance | |
| Group B | Patients with new diagnosis of advanced, evolving EE, worthy of medical treatment | |
| Group C | Patients with a previous diagnosis of advanced EE, already under active surveillance | |
| Group D | Patients with a previous diagnosis of advanced EE with ongoing medical treatment | |
| Group E | Patients with localized EHE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demographic description
To provide a demographic description of the population affected by advanced EHE
Measured: Through study completion, an average of 1 year
Patient status
To provide a description of clinical presentation, natural history, and treatment pattern in patients with advanced EHE
Measured: Through study completion, an average of 1 year
Tumor-related symptoms
To provide a description of tumour-related symptoms and their changes over time
Measured: Through study completion, an average of 1 year
Tumor-related pain
To provide a tumor-related pain assessment
Measured: Through study completion, an average of 1 year
Clinical prognosis
To prospectively identify clinical prognostic and predictive factors
Measured: Through study completion, an average of 1 year
radiological features
To describe the radiological features of the disease (group A, B, C, D, E)
Measured: Through study completion, an average of 1 year
correlation between radiological features and outcome
To correlate radiologic features with the outcome and the tested plasma levels of the cytokines and hormones (group A, B, C, D, E)
Measured: Through study completion, an average of 1 year
radiological response and systemic treatment
To assess radiologic response to systemic treatments by basing on RECIST 1.1 assessment (group B, D).
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2024
- Study start25 Feb 2021
- Primary completionFeb 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Clinical PresentationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Silvia Stacchiotti, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06680401
- Sponsor's protocol ID
- POEM
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2024
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev. 2014 Oct 13;8(2):259. doi: 10.4081/oncol.2014.259. eCollection 2014 Sep 23.
PubMed 25992243Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL, Chen HW, Pathan N, Krausz T, Dickson BC, Weinreb I, Rubin MA, Hameed M, Fletcher CD. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer. 2013 Aug;52(8):775-84. doi: 10.1002/gcc.22073. Epub 2013 Jun 5.
PubMed 23737213Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer. 2011 Aug;50(8):644-53. doi: 10.1002/gcc.20886. Epub 2011 May 16.
PubMed 21584898Lamar JM, Motilal Nehru V, Weinberg G. Epithelioid Hemangioendothelioma as a Model of YAP/TAZ-Driven Cancer: Insights from a Rare Fusion Sarcoma. Cancers (Basel). 2018 Jul 10;10(7):229. doi: 10.3390/cancers10070229.
PubMed 29996478Rosenbaum E, Jadeja B, Xu B, Zhang L, Agaram NP, Travis W, Singer S, Tap WD, Antonescu CR. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod Pathol. 2020 Apr;33(4):591-602. doi: 10.1038/s41379-019-0368-8. Epub 2019 Sep 19.
PubMed 31537895Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, Dail DH. Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J. 1998 Jul;12(1):89-96. doi: 10.1183/09031936.98.12010089.
PubMed 9701420Yousaf N, Maruzzo M, Judson I, Al-Muderis O, Fisher C, Benson C. Systemic treatment options for epithelioid haemangioendothelioma: the Royal Marsden Hospital experience. Anticancer Res. 2015 Jan;35(1):473-80.
PubMed 25550590Shiba S, Imaoka H, Shioji K, Suzuki E, Horiguchi S, Terashima T, Kojima Y, Okuno T, Sukawa Y, Tsuji K, Umemoto K, Asagi A, Todaka A, Ueno M, Ikeda M, Morizane C, Furuse J. Clinical characteristics of Japanese patients with epithelioid hemangioendothelioma: a multicenter retrospective study. BMC Cancer. 2018 Oct 19;18(1):993. doi: 10.1186/s12885-018-4934-0.
PubMed 30340559Agulnik M, Yarber JL, Okuno SH, von Mehren M, Jovanovic BD, Brockstein BE, Evens AM, Benjamin RS. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013 Jan;24(1):257-63. doi: 10.1093/annonc/mds237. Epub 2012 Aug 21.
PubMed 22910841Zheng Z, Wang H, Jiang H, Chen E, Zhang J, Xie X. Apatinib for the treatment of pulmonary epithelioid hemangioendothelioma: A case report and literature review. Medicine (Baltimore). 2017 Nov;96(45):e8507. doi: 10.1097/MD.0000000000008507.
PubMed 29137048Semenisty V, Naroditsky I, Keidar Z, Bar-Sela G. Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer. 2015 May 13;15:402. doi: 10.1186/s12885-015-1395-6.
PubMed 25967676Chevreau C, Le Cesne A, Ray-Coquard I, Italiano A, Cioffi A, Isambert N, Robin YM, Fournier C, Clisant S, Chaigneau L, Bay JO, Bompas E, Gauthier E, Blay JY, Penel N. Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the French Sarcoma Group (GSF/GETO). Cancer. 2013 Jul 15;119(14):2639-44. doi: 10.1002/cncr.28109. Epub 2013 Apr 15.
PubMed 23589078Maher ER, Robinson KN, Scoble JE, Farrimond JG, Browne DR, Sweny P, Moorhead JF. Prognosis of critically-ill patients with acute renal failure: APACHE II score and other predictive factors. Q J Med. 1989 Sep;72(269):857-66.
PubMed 2616731Radzikowska E, Szczepulska-Wojcik E, Chabowski M, Oniszh K, Langfort R, Roszkowski K. Pulmonary epithelioid haemangioendothelioma--interferon 2-alpha treatment--case report. Pneumonol Alergol Pol. 2008;76(4):281-5.
PubMed 18785134Stacchiotti S, Provenzano S, Dagrada G, Negri T, Brich S, Basso U, Brunello A, Grosso F, Galli L, Palassini E, Libertini M, Colia V, Gronchi A, Dei Tos AP, Crippa F, Morosi C, Pilotti S, Casali PG. Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database. Ann Surg Oncol. 2016 Sep;23(9):2735-44. doi: 10.1245/s10434-016-5331-z. Epub 2016 Jun 22.
PubMed 27334221
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Evaluation of Cytokines and Hormones as Biomarkers for Epithelioid Haemangioendothelioma and Generation of Patient-derived Preclinical Models to Assess the Activity of Anticancer Agents and Validate Novel Therapeutic Targets
- ClinicalTrials.gov ID
- NCT06680401
- Acronym / sponsor ID
- POEM
- Conditions
- Clinical Presentation, Natural History, Treatment Outcomes
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 8 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The EHE observational study was developed to obtain a high number of datas such as clinical presentation, natural history, and treatment outcomes, cto identificate cytokines and hormones as biomarkers and generate patient-derived preclinical models as a tool to assess the activity of anticancer agents and validate novel therapeutic targets
Detailed description
Epithelioid hemangioendothelioma (EHE) is an ultra-rare (incidence rate < 1/1000.000), translocated, vascular soft tissue sarcoma. It shows a pick of incidence in the 4th decade of life, and it is more commonly diagnosed in females, with reported disease onset during pregnancy.
Two specific translocations have been identified in EHE, representing an hallmark in diagnosis today: the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1) which is present in almost 90 % of cases, and the fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3), which can be found in around 10% of the patients. YAP and TAZ are well-defined downstream effectors in the Hippo pathway. Forced activation of YAP/TAZ is thought to drive EHE and contribute to key aspects of the cancer phenotype, including metastasis and fibrosis.
Most of the times, EHE presents as multifocal or metastatic at diagnosis, with lung, liver and bone being the more commonly involved. The clinical course ranges from cases naturally stable over time to those highly aggressive and rapidly fatal. Pleural effusion, lymph node metastases and pathologic features (nuclear pleomorphism, mitotic figures and presence of necrosis) have been reported to be associated with a worse outcome, but biological and molecular predictors are still lacking. In particular, there is a subgroup of EHE presenting with serosal involvement, typically associated with chronic mild fever, weight loss, asthenia, anorexia, severe disease- related pain, (more responsive to anti-inflammatory pain killers that morphine), and dyspnoea which seems to perform very poorly. The biological basis sustaining this presentation is completely unknown.
As of today, there are no reports available in literature providing a comprehensive description of the peculiar EHE radiological features, both for primary and metastatic disease at different sites, and their potential prognostic role has not been explored. In addition, there are no published data to indicate the optimal routine follow-up policy of surgically treated EHE patients with localised disease and the routine follow-up schedules differ across institutions. The appropriate frequency of imaging in cases suffering of distant metastases is also left to be determined.
Also, the definition of radiological progression and the assessment of treatment response in EHE remain major challenges. The appearance or worsening of serosal effusion, the changes in serosal involvement and the limited increase in size over a short-time interval in slow-growing variants are not promptly captured by Response Evaluation Criteria for Solid Tumor (RECIST) definition for disease progression. This makes the use of such criteria unsatisfactory in this complex disease and could potentially lead to a delay in progression recognition and treatment start. Similarly, being frequently observed in EHE under treatment, improvement of serosal effusion, reduction in size <30%, and correlation between radiology and symptoms should be taken into account when assessing treatment response.
Surgery is the mainstay of care in the local setting. Active surveillance can be a reasonable strategy for patients with naturally stable or asymptomatic, slowly progressive disease, reserving medical treatment to symptomatic or progressive cases.
Data on conventional chemotherapy in advanced EHE are limited to case reports and single-institution experiences and suggest a limited role for the drugs commonly used in adult-type soft tissue sarcomas. Signs of activity have been reported with the use of anti-angiogenics, including pazopanib, sorafenib, bevacizumab, alone or in combination with chemotherapy, and apatinib. Due to the peculiar natural history of the disease, the value of antiangiogenics and/or immunomodulatory agents has also been explored, with responses described with sirolimus, thalidomide, interferon, and celecoxib.
In absence of any active treatment available, EHE is a neglected disease, and the identification of new potentially active compounds, especially for patients affected by the more aggressive EHE variant. To this end, it looks to be of major importance to identify what is behind disease progression, the "inflammatory-like" disease presentation, and the prevalence of the disease in the female young population.
Several lines of evidence have highlighted the significance of inflammation at the local and/or systemic level in human tumor pathobiology. Indeed, inflammation can influence tumor progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation.
Estrogen signaling is mediated via several receptor proteins. In addition to the classical ERα and ERβ, the membrane-bound G-protein coupled estrogen receptor (GPER) mediates both the genomic and non-genomic effects of estrogen and has been implicated in the development of other tumors such as breast cancer. Interestingly, GPER stimulation activates YAP and TAZ as key effectors of the Hippo pathway. Insulin-like growth factor-1(IGF-1) has also been shown to regulate GPER expression and function, suggesting a crosstalk between growth factors and ERs The availability of translatable preclinical models of human EHE, able to properly recapitulate tumor biology and response to treatment of the clinical tumors, appears instrumental for the development of innovative and effective treatments. Patient-derived xenograft (PDX) models preserve the original histomorphological and molecular characteristics of the originating clinical tumors. We previously demonstrated the consistency between preclinical data obtained on PDXs of different soft-tissue sarcoma histotypes (solitary fibrous tumor, epithelioid sarcoma and dedifferentiated liposarcoma) and clinical results concerning the activity of several cytotoxic and molecularly targeted drugs, providing novel insight into the antitumor effect of different combinations that was instrumental to design novel clinical trials.
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Their proven deregulation in several types of human cancer, and the possibility to be reliably detected in both tissue and blood specimens, have prompted the assessment of miRNAs as novel cancer biomarkers21. No information is currently available on miRNA expression and function in EHE.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group A | – | –Patients newly diagnosed with advanced EE starting active surveillance |
| Group B | – | –Patients with new diagnosis of advanced, evolving EE, worthy of medical treatment |
| Group C | – | –Patients with a previous diagnosis of advanced EE, already under active surveillance |
| Group D | – | –Patients with a previous diagnosis of advanced EE with ongoing medical treatment |
| Group E | – | –Patients with localized EHE |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We plan to include at least 50 patients (range: 50-70) in 36 months, followed by a follow up time of 3 years.68 including The Royal Marsden Hospital.
Key inclusion criteria (4 listed)
- Histological diagnosis of EHE according to 2020 WHO classification, performed on biopsy or surgical specimen
- Signed informed consent
- Adequate patient compliance to treatment or follow up
- No age limit
Key exclusion criteria (1 listed)
- Impossibility to ensure adequate compliance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Demographic description
Time frame: Through study completion, an average of 1 year
To provide a demographic description of the population affected by advanced EHE
Patient status
Time frame: Through study completion, an average of 1 year
To provide a description of clinical presentation, natural history, and treatment pattern in patients with advanced EHE
Tumor-related symptoms
Time frame: Through study completion, an average of 1 year
To provide a description of tumour-related symptoms and their changes over time
Tumor-related pain
Time frame: Through study completion, an average of 1 year
To provide a tumor-related pain assessment
Clinical prognosis
Time frame: Through study completion, an average of 1 year
To prospectively identify clinical prognostic and predictive factors
radiological features
Time frame: Through study completion, an average of 1 year
To describe the radiological features of the disease (group A, B, C, D, E)
correlation between radiological features and outcome
Time frame: Through study completion, an average of 1 year
To correlate radiologic features with the outcome and the tested plasma levels of the cytokines and hormones (group A, B, C, D, E)
radiological response and systemic treatment
Time frame: Through study completion, an average of 1 year
To assess radiologic response to systemic treatments by basing on RECIST 1.1 assessment (group B, D).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
- Background: PubMed 25992243Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev. 2014 Oct 13;8(2):259. doi: 10.4081/oncol.2014.259. eCollection 2014 Sep 23.
- Background: PubMed 23737213Antonescu CR, Le Loarer F, Mosquera JM, Sboner A, Zhang L, Chen CL, Chen HW, Pathan N, Krausz T, Dickson BC, Weinreb I, Rubin MA, Hameed M, Fletcher CD. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer. 2013 Aug;52(8):775-84. doi: 10.1002/gcc.22073. Epub 2013 Jun 5.
- Background: PubMed 21584898Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer. 2011 Aug;50(8):644-53. doi: 10.1002/gcc.20886. Epub 2011 May 16.
- Background: PubMed 29996478Lamar JM, Motilal Nehru V, Weinberg G. Epithelioid Hemangioendothelioma as a Model of YAP/TAZ-Driven Cancer: Insights from a Rare Fusion Sarcoma. Cancers (Basel). 2018 Jul 10;10(7):229. doi: 10.3390/cancers10070229.
- Background: PubMed 31537895Rosenbaum E, Jadeja B, Xu B, Zhang L, Agaram NP, Travis W, Singer S, Tap WD, Antonescu CR. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod Pathol. 2020 Apr;33(4):591-602. doi: 10.1038/s41379-019-0368-8. Epub 2019 Sep 19.
- Background: PubMed 9701420Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, Dail DH. Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J. 1998 Jul;12(1):89-96. doi: 10.1183/09031936.98.12010089.
- Background: PubMed 25550590Yousaf N, Maruzzo M, Judson I, Al-Muderis O, Fisher C, Benson C. Systemic treatment options for epithelioid haemangioendothelioma: the Royal Marsden Hospital experience. Anticancer Res. 2015 Jan;35(1):473-80.
- Background: PubMed 30340559Shiba S, Imaoka H, Shioji K, Suzuki E, Horiguchi S, Terashima T, Kojima Y, Okuno T, Sukawa Y, Tsuji K, Umemoto K, Asagi A, Todaka A, Ueno M, Ikeda M, Morizane C, Furuse J. Clinical characteristics of Japanese patients with epithelioid hemangioendothelioma: a multicenter retrospective study. BMC Cancer. 2018 Oct 19;18(1):993. doi: 10.1186/s12885-018-4934-0.
- Background: PubMed 22910841Agulnik M, Yarber JL, Okuno SH, von Mehren M, Jovanovic BD, Brockstein BE, Evens AM, Benjamin RS. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013 Jan;24(1):257-63. doi: 10.1093/annonc/mds237. Epub 2012 Aug 21.
- Background: PubMed 29137048Zheng Z, Wang H, Jiang H, Chen E, Zhang J, Xie X. Apatinib for the treatment of pulmonary epithelioid hemangioendothelioma: A case report and literature review. Medicine (Baltimore). 2017 Nov;96(45):e8507. doi: 10.1097/MD.0000000000008507.
- Background: PubMed 25967676Semenisty V, Naroditsky I, Keidar Z, Bar-Sela G. Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer. 2015 May 13;15:402. doi: 10.1186/s12885-015-1395-6.
- Background: PubMed 23589078Chevreau C, Le Cesne A, Ray-Coquard I, Italiano A, Cioffi A, Isambert N, Robin YM, Fournier C, Clisant S, Chaigneau L, Bay JO, Bompas E, Gauthier E, Blay JY, Penel N. Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the French Sarcoma Group (GSF/GETO). Cancer. 2013 Jul 15;119(14):2639-44. doi: 10.1002/cncr.28109. Epub 2013 Apr 15.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Silvia Stacchiotti principal investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Clinical Presentation and Natural History, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Silvia Stacchiotti (0223902803, Silvia.Stacchiotti@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Demographic description (time frame: Through study completion, an average of 1 year). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06680401, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.